P450 isoforms in a murine macrophage cell line, RAW264.7, and changes in the levels of P450 isoforms by treatment of cells with lipopolysaccharide and interferon-γ

Nakamura, Mayumi; Imaoka, Shingi; Amano, Fumio; Funae, Yoshihiko

doi:10.1016/s0167-4838(98)00052-1

Cited by 13 publications

(7 citation statements)

References 23 publications

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“…We tried to identify the enzyme responsible for formation of the P1 metabolite. Earlier PCR-based expression analysis revealed the presence of only two CYP450 enzymes in macrophages (46). Here, we found seven macrophage CYP450s, but only two were upregulated in M2-polarized macrophages, CYP2E1 and CYP1B1.…”

Section: Discussionsupporting

confidence: 43%

Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages

Kriska

Thomas

Falck

et al. 2018

Journal of Lipid Research

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Polarization of macrophages to proinflammatory M1 and to antiinflammatory alternatively activated M2 states has physiological implications in the development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction. Cultured M2 macrophages metabolized externally added [C]12(S)-HETE into more polar metabolites, while M1 macrophages had little effect on the catabolism. The major metabolites were identified by mass spectrometry as (ω-1)-hydroxylation and β-oxidation products. The conversion was inhibited by both peroxisomal β-oxidation inhibitor, thioridazine, and cytochrome P450 inhibitors. Quantitative PCR analysis confirmed that several cytochrome P450 enzymes (CYP2E1 and CYP1B1) and peroxisomal β-oxidation markers were upregulated upon M2 polarization. The identified 12,19-dihydroxy-5,8,10,14-eicosatetraenoic acid and 8-hydroxy-6,10-hexadecadienoic acid metabolites were tested on abdominal aortic rings for biological activity. While 12(S)-HETE enhanced vasoconstrictions to angiotensin II from 15% to 25%, the metabolites did not. These results indicate that M2, but not M1, macrophages degrade 12(S)-HETE into products that no longer enhance the angiotensin II-induced vascular constriction, supporting a possible antihypertensive role of M2 macrophages.

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Section: Discussionsupporting

confidence: 43%

Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages

Kriska

Thomas

Falck

et al. 2018

Journal of Lipid Research

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“…A hypothesis to explain that we did not detect any DNA-BPDE adducts in RAW 264.7 macrophages would be that these cells do not have the capacity to metabolize B[a]P to BPDE. However, the RAW 264.7 cell line has been shown to express active P450 cytochromes, which are responsible for this metabolization [45]. Moreover, we did not observe any BPDE-DNA adduct, even when RAW 264.7 cells were directly exposed to BPDE.…”

Section: Discussioncontrasting

confidence: 46%

Toxicity to RAW264.7 Macrophages of Silica Nanoparticles and the E551 Food Additive, in Combination with Genotoxic Agents

et al. 2020

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Synthetic amorphous silica (SAS) is used in a plethora of applications and included in many daily products to which humans are exposed via inhalation, ingestion, or skin contact. This poses the question of their potential toxicity, particularly towards macrophages, which show specific sensitivity to this material. SAS represents an ideal candidate for the adsorption of environmental contaminants due to its large surface area and could consequently modulate their toxicity. In this study, we assessed the toxicity towards macrophages and intestinal epithelial cells of three SAS particles, either isolated SiO2 nanoparticles (LS30) or SiO2 particles composed of agglomerated-aggregates of fused primary particles, either food-grade (E551) or non-food-grade (Fumed silica). These particles were applied to cells either alone or in combination with genotoxic co-contaminants, i.e., benzo[a]pyrene (B[a]P) and methane methylsulfonate (MMS). We show that macrophages are much more sensitive to these toxic agents than a non-differenciated co-culture of Caco-2 and HT29-MTX cells, used here as a model of intestinal epithelium. Co-exposure to SiO2 and MMS causes DNA damage in a synergistic way, which is not explained by the modulation of DNA repair protein mRNA expression. Together, this suggests that SiO2 particles could adsorb genotoxic agents on their surface and, consequently, increase their DNA damaging potential.

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“…Both cytochrome P450‐dependent monooxygenases and uridine diphosphate glucuronosyltransfease contribute to the metabolism of propofol into 4‐hydroypropofol 18. These endogenous enzymes are detectable in Raw 264.7 cells 19,20. Therefore, the metabolism of propofol in macrophages by these endogenous enzymes may be another reason to explain the decreasing effects of this anesthetic agent on the mitochondrial membrane potential, ATP synthesis, and cell migration.…”

Section: Discussionmentioning

confidence: 99%

Propofol Specifically Inhibits Mitochondrial Membrane Potential but Not Complex I NADH Dehydrogenase Activity, Thus Reducing Cellular ATP Biosynthesis and Migration of Macrophages

Tai

Chen

et al. 2005

Annals of the New York Academy of Sciences

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Propofol is a widely used intravenous anesthetic agent. Our previous study showed that a therapeutic concentration of propofol can modulate macrophage functions. Mitochondria play critical roles in the maintenance of macrophage activities. This study attempted to evaluate further the effects of mitochondria on the propofol-induced suppression of macrophage functions using mouse macrophage-like Raw 264.7 cells as the experimental model. Macrophages were exposed to a clinically relevant concentration of propofol for 1, 6, and 24 h. Analysis by the Trypan blue exclusion method revealed that propofol was not cytotoxic to macrophages. Exposure of macrophages to propofol did not affect mitochondrial NADH dehydrogenase activity of complex I. However, analysis of flow cytometry showed that propofol significantly decreased the mitochondrial membrane potential of macrophages. Cellular levels of ATP in macrophages were significantly reduced after propofol administration. In parallel with the dysfunction of mitochondria, the chemotactic analysis showed that exposure to propofol significantly inhibited the migration of macrophages. This study shows that a therapeutic concentration of propofol can specifically reduce the mitochondrial membrane potential, but there is no such effect on complex I NADH dehydrogenase activity. Modulation of the mitochondrial membrane potential may decrease the biosynthesis of cellular ATP and thus reduce the chemotactic activity of macrophages. This study provides in vitro data to validate mitochondrial dysfunction as a possible critical cause for propofol-induced immunosuppression of macrophage functions.

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P450 isoforms in a murine macrophage cell line, RAW264.7, and changes in the levels of P450 isoforms by treatment of cells with lipopolysaccharide and interferon-γ

Cited by 13 publications

References 23 publications

Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages

Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages

Toxicity to RAW264.7 Macrophages of Silica Nanoparticles and the E551 Food Additive, in Combination with Genotoxic Agents

Propofol Specifically Inhibits Mitochondrial Membrane Potential but Not Complex I NADH Dehydrogenase Activity, Thus Reducing Cellular ATP Biosynthesis and Migration of Macrophages

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